The AccellTM gene delivery system (gene gun) was used to deliver gold particles coated with HIV-1LA1 and SIVmac239 expression constructs into the epidermis of rhesus macaques, resulting in the elicitation of env and gag-specific humoral responses. One microgram of vector DNA per dose was sufficient to induce immune responses in monkeys using SIVmac239 gp160 and gp120 vectors driven by the CMV-intron A promoter. Several parameters including the identity of the vector, the length of the rest period between immunizations, the number of immunizations, and the amount of DNA per immunization, are all important in designing an optimal DNA immunization regimen. In addition, gene-gun based DNA immunization using low efficiency expression vectors is an effective means of priming for the induction of vigorous antibody responses in macaques following boosting with recombinant subunits.